Injectable Biodegradable Silica Depot: Two Months of Sustained Release of the Blood Glucose Lowering Peptide, Pramlintide.

Puneet Tyagi,Lasse Leino,Victor G Howard,Mika Koskinen,Helen Brant,Sanjay Sarkhel,Dominic Corkill,Shimona Madalli,Asha Seth,Sarah Will,Jari Mikkola

doi:10.3390/pharmaceutics14030553

Puneet Tyagi, Lasse Leino + Show 9 more

Open Access

https://doi.org/10.3390/pharmaceutics14030553

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Abstract

Diabetes mellitus is a major healthcare challenge. Pramlintide, a peptide analogue of the hormone amylin, is currently used as an adjunct with insulin for patients who fail to achieve glycemic control with only insulin therapy. However, hypoglycemia is the dominant risk factor associated with such approaches and careful dosing of both drugs is needed. To mitigate this risk factor and compliance issues related to multiple dosing of different drugs, sustained delivery of Pramlintide from silica depot administered subcutaneously (SC) was investigated in a rat model. The pramlintide-silica microparticle hydrogel depot was formulated by spray drying of silica sol-gels. In vitro dissolution tests revealed an initial burst of pramlintide followed by controlled release due to the dissolution of the silica matrix. At higher dosing, pramlintide released from subcutaneously administered silica depot in rats showed a steady concentration of 500 pM in serum for 60 days. Released pramlintide retained its pharmacological activity in vivo, as evidenced by loss of weight. The biodegradable silica matrix offers a sustained release of pramlintide for at least two months in the rat model and shows potential for clinical applications.

Highlights

Diabetes mellitus poses a major global health challenge, with estimates of the human population affected to touch a staggering 783 million by 2045 [1]
The present study shows the utility of a silica-based matrix for sustained control rerelease of pramlintide in a rat model for two months
The results show that sustained release release of pramlintide silica depot be achieved to maintain plasma concentration oflevels pramlintide fromHowever, silica depot can be achieved maintain plasma concentration levels of 500 pM

Summary

Introduction

Diabetes mellitus poses a major global health challenge, with estimates of the human population affected to touch a staggering 783 million by 2045 [1]. It results from a complete deficiency of insulin (type 1) or impaired insulin secretion (type II) due to β-cell dysfunction. The disease imposes a huge burden on the healthcare system and accounts for more than 10% of its spending [1]. It manifests multiple complications, and an active diabetes care and management program aims at regulating the blood glycemic levels [5]. Therapeutic drugs have some limitations, they continue to be the main choice in the active

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